CN114533582A - A composition for use around the eye comprising a plurality of osmoprotectants - Google Patents
A composition for use around the eye comprising a plurality of osmoprotectants Download PDFInfo
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Abstract
The present application provides a periocular composition comprising a plurality of osmoprotectants, comprising a plurality of osmoprotectants selected from erythritol, ectoin, L-carnitine, etc., and a xanthophyll or rhamnolipid component. The composition can effectively protect skin cells around eyes from being damaged by blue light, provides a protective effect on a hypertonic environment for corneal epithelial cells, and is expected to be used for treating xerophthalmia and asthenopia, even eye symptoms such as macular degeneration and the like.
Description
Technical Field
The application belongs to the field of cosmetics and ophthalmic medicaments, and particularly provides a composition for caring skin around eyes, which comprises various osmotic pressure protective agents selected from erythritol, ectoine, L-carnitine and the like and a lutein or rhamnolipid component.
Background
The skin and tissues around our eyes receive different degrees of damage every day due to factors such as light, pollution and the like. Furthermore, tears, particularly hypertonic tears in patients with ocular diseases such as dry eye, also cause damage to corneal epithelial cells and skin cells around the eye.
The skin around the eyes naturally repairs general injuries, such as increasing the immunity of the skin to remove or reduce inflammation caused by bacterial infection. Therefore, the best method for daily maintenance of the periocular skin is to maintain the periocular skin by a natural or bionic method, protect ocular tissues and cells under the periocular skin, improve the ocular surface homeostasis and metabolism, alleviate asthenopia, delay the progression of myopia and reduce the damage of fundus macular tissues. Finding a suitable combination of active ingredient with an osmoprotectant is the main way to improve the protective effect.
Eye protection efficacy of lutein: (1) the chemical structure of lutein contains eight isoprene units, which constitutes a powerful blue filter. The blue light is blocked and directly irradiated on the retina macular tissue, and the killing power of the blue light with the wavelength of 300-500nm to the fundus tissue is the maximum; (2) the lutein has good antioxidant capacity, can remove free radicals generated by blue light damage so as to further protect the tissues of the anterior eye or the fundus oculi, (3) the lutein also has the function of anti-inflammation, and can reduce the expression of inflammatory cytokines and matrix metalloproteinase caused by ultraviolet light or environmental pollution after long-term use so as to further protect collagen, (4) the color of the skin depends on the distribution content and density of melanin granules generated by melanocytes on the skin around the eyes, for example, the lutein can effectively delay the tyrosine from being oxidized and metabolized into melanin. In a word, the effect of correctly and long-term use of lutein on reducing the risks of eye diseases such as macular degeneration, cataract, diabetic retinopathy and the like is proved slowly and continuously, and more people begin to pay attention to the lutein, and the lutein is an important component of the health of people.
Rhamnolipid is a surfactant with biological metabolism property, and is also a biological preservative and biological emulsifier. Rhamnolipids can reduce the surface activity of the formula (from 72mN/m to around 30). So that the rhamnolipid can remove the environmental pollutants deposited on the skin around the eyes. Rhamnolipid is a biosurfactant produced by a biological fermentation method. It has little irritation, and is a biological antifungal agent. Besides good emulsification, it can also remove foam in large-scale production, increase canning speed and reduce production time.
We generally refer to organic small molecule compatilizers osmoprotectants having these properties. Another characteristic of the osmotic pressure protective agents is that the osmotic pressure protective agents can freely enter and exit cells, and the osmotic pressure protective agents are not like sodium chloride which needs the assistance of other factors when entering and exiting cell membranes, and can bring out and bring in water molecules to destroy the normal volume of the cells to cause the final necrosis of the cells. Even some osmoprotectants can be determined whether to enter or exit cells by evaluating the intracellular pressure, so 20-30% of the osmoprotectants are not irritating to the periocular skin and ocular surface and exhibit unique biocompatibility. The prescription of the invention utilizes the concept of bionics of the osmotic pressure protective agent, balances and adjusts the homeostasis of the skin and tissues on the ocular surface, protects and nurses the skin and tissues around the eye to the maximum extent, and even achieves a certain treatment effect.
The osmotic pressure protective agent disclosed by the invention further protects the stability and health of sebum through mutual synergistic action on the basis of protecting surface cells. The L-carnitine can effectively induce the synthesis of collagen and elastin, and the ectoin can increase the softness of healthy sebum so as to be uniformly distributed on the surface, so that the moisture retention and the prevention of the invasion of harmful microorganisms can be achieved only by ensuring the integrity of the sebum. The healthy epidermis homeostasis is more beneficial to the transdermal absorption of the active ingredient erythritol disclosed by the invention, the degradation of collagen is reduced, and the function of protecting the skin elasticity of the collagen is ensured.
Erythritol is not only an osmoprotectant but also a better antioxidant. The main function is to prevent skin cell necrosis caused by skin hypertonicity, especially skin hypertonicity caused by ultraviolet illumination. The invention mainly utilizes the moisturizing effect of erythritol to delay the damage of collagen.
Excessive fat can form orange peel lines, especially under the periocular skin, causing a discontinuity in the appearance of the epidermis. L-carnitine can inhibit fat synthesis, thereby reducing orange peel formation. Especially, the eye cream is combined with ectoine, and the skin around the eyes looks healthy and active after the eye cream is used. The ectoin can increase the softness of fat, so that the fat is uniformly distributed under the skin, the formation of orange peel wrinkles is reduced, moisture is preserved, and the damage of ultraviolet irradiation to the skin around eyes is reduced.
Ectoin can carry 9 water molecules, increases intermolecular distance, protects cells by enhancing the mobility of cell membrane fat, and increases the fluidity of skin lipid to reduce the loss of epidermal water.
The L-carnitine can directly reduce the damage of ultraviolet rays to the skin around eyes, and the long-term deficiency of the L-carnitine in eye tissues and tears can cause eye diseases and even cataract.
Disclosure of Invention
In order to solve the above problems, the present invention provides a composition comprising various osmoprotectants, which further protects the stability and health of sebum through the synergistic interaction between each other on the basis of protecting surface cells. The L-carnitine can effectively induce the synthesis of collagen and elastin; ectoin increases the softness of healthy sebum and thus distributes evenly over the surface, preserving moisture and preventing the invasion of harmful microorganisms only if the integrity of the sebum is guaranteed. The healthy epidermis is in a constant state, so that the skin can be absorbed transdermally by the erythritol serving as the active ingredient, the degradation of collagen is reduced, and the function of protecting the skin elasticity of the collagen is ensured.
In one aspect, the present application provides a periocular skin or ophthalmic composition comprising an osmoprotectant selected from one or more of erythritol, ectoine, and l-carnitine.
Further, the composition is a liquid formulation.
Further, the concentration of the osmotic pressure protective agent is 0.01-30%.
Further, the composition comprises 0.01% to 1%, preferably 0.1% erythritol, 0.01% to 1%, preferably 0.1% ectoin and 0.01% to 1%, preferably 0.1% l-carnitine.
Further, the composition further comprises lutein and/or rhamnolipids.
Further, the composition comprises 0.01% -1%, preferably 0.01% lutein.
Further, the composition comprises 0.01% -5%, preferably 1% rhamnolipid.
Further, the composition further comprises an adjuvant selected from the group consisting of a buffer, an emulsifier, an antioxidant, and a preservative.
Further, the composition further comprises an ingredient selected from the group consisting of honey locust seed extract, retinol/saccharomyces polypeptides, sodium hyaluronate, panthenol, peppermint leaf extract, cyanocobalamin, magnesium PCA, manganese PCA, sodium PCA, tetrahydromethylpyrimidine carboxylic acid, ceramides, haematococcus pluvialis extract, plantain flower, centella asiatica extract, brussels sprout extract, cabbage italica bud extract, sunflower bud extract, canola bud extract, cranberry fruit extract, corn kernel extract, ascorbyl acid, lotus water, echeveria water, ganoderma sinensis extract, gentian extract, matrimony vine fruit extract, p-hydroxyacetophenone, hexylene glycol.
In another aspect, the application provides an application of the composition in preparing an eye skin repair product.
In another aspect, the present application provides the use of the above composition for the preparation of a medicament for treating or preventing dry eye or asthenopia.
Drawings
FIG. 1 is a graph of the protective effect of various groups of xanthophylls and osmoprotectants on skin keratinocytes.
FIG. 2 is a graph of the protective effect of various groups of xanthophylls and osmoprotectant on skin fibroblasts.
FIG. 3 is a graph showing the protective effect of various groups of osmoprotectants on corneal epithelial cells in a hypertonic environment.
FIG. 4 is a graph showing the protective effect of various groups of osmoprotectants and surfactants on corneal epithelial cells in a hypertonic environment.
FIG. 5 is a graph of the effect of osmoprotectant on corneal epithelial cell IL-6 cytokine expression.
Detailed description of the preferred embodiments
Principal materials and reagents
Human skin keratinocytes: ATCC CRL-2404; (according to the ATCC guidelines, the medium essentially contains eagle's basal medium, 5ng/ml EGF (Epidermal Growth Factor), 2mM L-glutamine, 10000 units of penicillin, 10mg/ml streptomycin)
Human skin fibroblasts: ATCC CRL-2115 (medium mainly comprising eagle's basic medium, 10% FBS, 10000 units of penicillin, 10mg/ml streptomycin according to ATCC's guidelines);
human corneal epithelial cells (HCEpC): CRL-11135, HCE-2, ACTT
Lutein: american jestimine
Erythritol: jiaji of America (Cargill)
Ectoin: bitop in Germany
L-carnitine: swiss dragon sand (Lonza)
Rhamnolipid: shanghai-sourced leaf Biotechnology, Inc.;
tween 80: shanxi brocade medicinal adjuvant Co., Ltd;
poloxamer F68: BASF;
other reagents are made of domestic or imported products meeting corresponding standards.
Cell survival experiments under blue light:
cultured human skin keratinocytes were placed in 96-well culture dishes at a cell density of about 1X 10 per ml5Cells (culture medium containing lutein, osmoprotectant, etc., lutein was added after 2.5mg/ml solution using DSMO, others were added directly) were placed in 96-well dishes under 470nm blue light for 12 hours (1900 Lux). After trypan blue staining, the cells were observed and the number of surviving cells was recorded.
Cell survival experiments under hypertonic conditions:
corneal epithelial cells were seeded in a 96-well plate (EpiLife medium), cultured for 72 hours and aspirated, replaced with fresh baseline control medium (EpiLife medium) and cultured for another 24 hours. Incubate for 4 hours with EpiLife medium, wash once with EpiLife medium and then expose to baseline control EpiLife medium (310mOsm/kg) or hypertonic EpiLife medium (450mOsm/kg) with sodium chloride adjusted osmolality for 20 hours (various osmolality adjusting agents, surfactants were added to the medium). Alarm blue detects cell activity.
Applicants conducted numerous quantitative and proportional experiments, and only some representative experimental results are shown herein.
Example 1 protective Effect of lutein in combination with an osmoprotectant on skin keratinocytes and skin fibroblasts
The other ingredients added to the cell culture medium are shown in the following table:
the results are shown in figures 1, 2 and indicate that the combination of the osmoprotectant and lutein protects skin keratinocytes and skin fibroblasts better than either the osmoprotectant or lutein alone, reducing the damage from blue light exposure. The combined effect of the three types of osmotic pressure protection is particularly pronounced. This may result from different effects of different osmoprotectants on the cells.
EXAMPLE 2 protective Effect of osmoprotectant on corneal epithelial cells
Although the relevant product of the applicant is an eye spray at present, on one hand, the spray inevitably enters eyes to contact cells such as corneal epithelial cells and the like during use, and hypertonic tear also often contacts the skin around the eyes for a long time; on the other hand, the applicant also wanted to further extend the ophthalmic spray to other ophthalmic formulations that directly contact the eye (dry eye and asthenopia patients have tears with osmotic pressures much higher than normal tears). The applicant has therefore further investigated the protective effect of the osmoprotectant on corneal epithelial cells and the other components added to the cell culture medium are shown in the following table:
the results are shown in fig. 3 and show that although the combined use of three osmoprotectants largely avoids damage to corneal epithelial cells from the hypertonic environment, the metabolic activity of corneal epithelial cells is still greatly affected. It is necessary to investigate further the addition of other ingredients.
Example 3 we then attempted to add surfactants either individually or in combination with the above formulations.
The results are shown in fig. 4, and show that the addition of the surfactant alone is beneficial to the activity of the cells, but the effect is not significant, and no obvious difference exists among various surfactants; however, the combination of surfactants, in particular rhamnolipids, with the aforementioned osmoprotectants can very well enhance the protective effect of the osmoprotectants such that the corneal epithelial cells easily survive/remain active in a hypertonic environment. Products for caring eye skin, such as eye spray, prepared from osmotic pressure protective agent (L-carnitine, erythritol, ectoine) or osmotic pressure protective agent and surfactant rhamnolipid are capable of reducing irritation, damage and dryness of eye skin due to high salt, further reducing irritation and damage to eye surface layer cells, maintaining metabolic activity and integrity of related cells, changing eye surface homeostasis, reducing eye fatigue, and reducing incidence of eye surface inflammation.
Example 4
The results are shown in FIG. 5, and indicate that the osmoprotectant may reduce the increase of cytokine IL-6 due to high osmotic tear fluid. Viewed from another perspective, the reduction of the corneal upper surface cytokine IL-6 again demonstrates that the osmoprotectant is likely to act as an ocular surface anti-inflammatory agent and to improve ocular surface homeostasis.
EXAMPLE 5 preparation of actual pharmaceutical Agents
Based on the above formula containing erythritol, ectoin, l-carnitine and or rhamnolipids, we formulated the product examples with additional ingredients:
example 1
The components: water, seawater, lutein, gleditsia sinensis seed extract, retinol/saccharomyces polypeptides, sodium hyaluronate, panthenol, peppermint leaf extract, cyanocobalamin, magnesium PCA, manganese PCA, sodium PCA, tetrahydromethylpyrimidine carboxylic acid, ceramide, haematococcus pluvialis extract, plantain flower, centella asiatica extract, lotus water, aegyptia blue water lily flower water, ganoderma china extract, gentian extract, lycium barbarum fruit extract, p-hydroxyacetophenone, hexylene glycol.
The efficacy is as follows: the product is added with various eye skin nutrient elements and trace elements such as gleditsia sinensis seed extract, lutein, retinol/zymophyte polypeptide, panthenol, vitamin B12 (cyanocobalamine), magnesium, manganese, sodium and the like, is supplemented with refined extracts of plants such as haematococcus, centella asiatica, lucid ganoderma, gentian and medlar and has the effects of moistening and moisturizing, is blended with French rose coastal sea spring water, is loaded with superfine fog beads, supplements moisture, is sprayed and elastic for moistening, and is subjected to layer-by-layer penetration repair, so that the skin around the eyes is tight and fine, and the eyes are bright.
Example 2
The components: water, seawater, lutein, gleditsia sinensis seed extract, retinol/saccharomyces polypeptides, sodium hyaluronate, panthenol, peppermint leaf extract, cyanocobalamin, magnesium PCA, manganese PCA, sodium PCA, tetrahydromethylpyrimidine carboxylic acid, ceramides, broccoli extract, italian cabbage bud extract, sunflower bud extract, canola bud extract, ganoderma lucidum extract, gentian extract, ningxia wolfberry fruit extract, p-hydroxyacetophenone, hexylene glycol.
The efficacy is as follows: the product is added with various eye skin nutrient elements and trace elements such as gleditsia sinensis seed extract, lutein, retinol/zymophyte polypeptide, panthenol, vitamin B12 (cyanocobalamine), magnesium, manganese, sodium and the like, is supplemented with plant refined extracts such as broccoli, lucid ganoderma, gentian, medlar and the like, is blended with Faguo rose coastal sea spring water, is loaded with superfine fog beads, and is sprayed for refreshing and moistening repair to ensure that the skin around the eyes are smooth and compact and the eyes are smooth and bright.
Example 3:
the components: water, seawater, lutein, Gleditsia sinensis seed extract, retinol/Saccharomyces polypeptides, sodium hyaluronate, panthenol, peppermint leaf extract, cyanocobalamin, magnesium PCA, manganese PCA, sodium PCA, tetrahydromethylpyrimidine carboxylic acid, ceramide, cranberry fruit extract, corn kernel extract, Ascophyllum nodosum extract, parsley extract, grapefruit extract, ascorbic acid, Ganoderma sinensis extract, gentian extract, Lycium barbarum fruit extract, p-hydroxyacetophenone, hexylene glycol.
The efficacy is as follows: the product is added with various eye skin nutrient elements and trace elements such as gleditsia sinensis seed refined extract, lutein, retinol/zymophyte polypeptide, vitamin B5 (panthenol), magnesium, manganese, sodium and the like, is supplemented with plant refined extract such as cowberry fruit, corn kernel, ascophyllum nodosum, parsley, lucid ganoderma and the like, is blended with French rose coastal sea spring water, is elaborately compounded with sodium hyaluronate, mint and erythritol, carries ultrafine fog beads, and has the effects of lasting care, relieving and repairing skin around eyes and moistening and brightening eyes.
It is to be understood that the above examples are illustrative only for the purpose of clarity of description and are not limiting of the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (11)
1. A composition for the periocular use comprising a plurality of osmoprotectants, wherein the composition comprises one or more osmoprotectants selected from erythritol, ectoin, and L-carnitine.
2. The composition of claim 1, which is a liquid formulation.
3. The osmoprotectant according to claim 1, having a concentration of 0.01% to 30%.
4. The composition according to claim 3, comprising 0.01% to 1%, preferably 0.1% erythritol, 0.01% to 1%, preferably 0.1% ectoine and 0.01% to 1%, preferably 0.1% L-carnitine.
5. The composition according to claim 2, further comprising lutein and/or rhamnolipids.
6. A composition according to claim 5, comprising 0.01% -1%, preferably 0.01% lutein.
7. A composition according to claim 5 comprising 0.01% -5%, preferably 1% rhamnolipids.
8. The composition according to any one of claims 1-7, further comprising an adjuvant selected from the group consisting of buffers, emulsifiers, antioxidants, preservatives.
9. The composition of any one of claims 1-8, further comprising an ingredient selected from the group consisting of a gleditsia sinensis seed extract, retinol/saccharomyces polypeptides, sodium hyaluronate, panthenol, peppermint leaf extract, cyanocobalamin, magnesium PCA, manganese PCA, sodium PCA, tetrahydromethylpyrimidine carboxylic acid, ceramide, haematococcus pluvialis extract, plantain flower, centella asiatica extract, brussels sprout extract, cabbage italian bud extract, sunflower bud extract, rape bud extract, cranberry fruit extract, corn kernel extract, paulownia extract, parsley extract, grapefruit extract, ascorbic acid, lotus water, aegyptian water, ganoderma sinensis extract, gentian extract, lycium ninghamii fruit extract, p-hydroxyacetophenone, hexanediol.
10. Use of a composition according to any one of claims 1 to 9 for the preparation of an ocular skin repair product.
11. Use of a composition according to any one of claims 1 to 10 for the manufacture of a medicament for the treatment or prevention of dry eye or asthenopia.
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